Fig. 1

Schematic representation depicting different strategies of protein suppression. a PROTAC recruits an E3 ligase to a POI followed by polyubiquitination of the POI by an E2 conjugating enzyme. The polyubiquitinated POI is recognized and degraded by the proteasome. Once the POI is degraded, the PROTAC molecule can be recycled to induce the next round of POI degradation, thus working in a sub-stoichiometric manner. b A small molecule inhibitor (SMI) typically binds at the active site of a POI to inhibit the enzymatic functions of the POI. c A monoclonal antibody (mAb) binds to a cell surface receptor to block the signal transduction stimulated by a ligand, a growth factor or a cytokine. d siRNA binds to its targeted mRNA transcript in a complementary manner to induce mRNA cleavage and consequently translational suppression. e An antibody-PROTAC conjugate (Ab-PROTAC) is designed by linking a PROTAC to a mAb. Once an Ab-PROTAC binds to its cell surface receptor, it is internalized into the cytosol through endosomes. In the cytosol, an active PROTAC releases from Ab-PROTAC through lysosomal pathway which induces the degradation of POI